The BioScientisthttps://thebioscientist.org Unleashing the World of Biosciences Tue, 19 Mar 2019 07:59:10 +0000 en-US hourly 1 https://wordpress.org/?v=5.1.1https://i1.wp.com/thebioscientist.org/wp-content/uploads/2017/11/DpBio-e1509873638123.jpg?fit=32%2C32&ssl=1The BioScientisthttps://thebioscientist.org 3232138129567Scientists identify the brain circuit responsible for alcohol cravingshttps://thebioscientist.org/2019/03/19/scientists-identify-the-brain-circuit-responsible-for-alcohol-cravings/ https://thebioscientist.org/2019/03/19/scientists-identify-the-brain-circuit-responsible-for-alcohol-cravings/#respondTue, 19 Mar 2019 07:52:07 +0000https://thebioscientist.org/?p=2453Scientists at Scripps Research have found that they can reverse the desire to drink in alcohol-dependent rats–with the flip of a switch. The researchers were able to use lasers to temporarily inactivate a specific neuronal population, reversing alcohol-seeking behavior and even reducing the physical symptoms of withdrawal. “This discovery is exciting–it means we have another …

]]>Scientists at Scripps Research have found that they can reverse the desire to drink in alcohol-dependent rats–with the flip of a switch. The researchers were able to use lasers to temporarily inactivate a specific neuronal population, reversing alcohol-seeking behavior and even reducing the physical symptoms of withdrawal.

“This discovery is exciting–it means we have another piece of the puzzle to explain the neural mechanism driving alcohol consumption,” says Olivier George, PhD, an associate professor at Scripps Research and senior author of the new study, published March 18, 2019 in the journal Nature Communications.

Although the laser treatment is far from ready for human use, George believes identifying these neurons opens the door to developing drug therapies or even gene therapies for alcohol addiction.

“We need compounds that are specific to this neuronal circuitry,” George says.

According to the National Institute on Alcohol Abuse and Alcoholism, more than 15.1 million adults in the United States suffer from alcohol use disorder. Previous work at Scripps Research has shown that transitioning from casual drinking to dependent drinking occurs alongside fundamental changes in how the brain sends signals. These signals drive the intense cravings that make it so difficult for many people to scale back their alcohol consumption.

George and his colleagues have been hunting for the brain cells that driving drinking in an alcohol-addicted rat model. In 2016, they reported that they had found a possible source: a neuronal “ensemble,” or group of connected cells in a brain region called the central nucleus of the amygdala (CeA). This finding marked major progress in mapping the brain, but the researchers needed to characterize the identity of the neurons in this ensemble.

For the new study, they tested the role of a subset of neurons in the ensemble, called corticotropin-releasing factor (CRF) neurons. The George laboratory had found that these CRF neurons make up 80 percent of the ensemble. Were these neurons the masterminds driving alcohol cravings?

The researchers studied these neurons using optogenetics, a technique that involves the use of light to control cells in living tissue. Rats used in this study were surgically implanted with optic fibers aimed to shine light on the CRF neurons–to inactivate them at the flip of a switch.

First, the scientists established a baseline for how much the rats would drink before they got addicted to alcohol. The rats drank little this point–the equivalent of a glass of wine or one beer for a human. The scientists then spent several months increasing consumption in these rats to establish alcohol dependence.

The researchers then withdrew the alcohol, prompting withdrawal symptoms in the rats. When they offered alcohol again, the rats drank more than ever. The CeA neuronal ensemble was active, telling the rats to drink more.

Then the scientists flipped on the lasers to inactivate the CRF neurons–and the results were dramatic. The rats immediately returned to their pre-dependent drinking levels. The intense motivation to drink had gone away. Inactivating these neurons also reduced the physical symptoms of withdrawal, such as abnormal gait and shaking.

“In this multidisciplinary study, we were able to characterize, target and manipulate a critical subset of neurons responsible for excessive drinking.” says Giordano de Guglielmo, PhD, first author of the study and staff scientist at Scripps Research.

“This was a team effort, and while we used challenging techniques, working with experts in the field and with the right tools, made everything easier and enjoyable.”

The effect was even reversible. Turn off the lasers, and the rats returned to their dependent behavior.

From a basic science standpoint, this breakthrough is huge: It reveals wiring in the brain that drives a specific, destructive behavior. George says the next step in translating this work to humans is to find a way to selectively inhibit only these specific CRF neurons, perhaps using a novel or repurposed compound identified using high-throughput screening of large libraries of compounds.

Meanwhile, de Guglielmo plans to take a closer look at the signaling pathways in the brain affected when the CRF neurons are deactivated. The new study shows that reduced drinking is tied to the CRF neurons that send projections to reach another brain region called the bed nucleus of the stria terminalis. De Guglielmo thinks other projections from these neurons may have different roles in alcohol addiction. He is also interested in identifying the role of these brain circuits in opioid addiction.

An autoimmune disorder occurs when the immune system attacks healthy body tissues. The exact reason behind autoimmune disease is still unknown. One theory is that certain microorganisms or drugs may trigger the change in immune response. Some common autoimmune diseases are Addison’s disease, dermatomyositis, Graves’ disease, Rheumatoid arthritis, Type 1 diabetes etc.

What are Foxp1 proteins?

Foxp1 also known as Forkhead box protein is coded by Foxp1 gene. The diseases that are known associated with these protein are mental retardation with language impairment, lymphoma etc. This protein is necessary for proper development in brain, heart and liver in mammals. It is the member of FOX family of transcription factors. Basically it is a transcription factor and particularly transcriptional repressor. Foxp1 has three important roles, these include regulation of cardiac myocyte maturation, outflow tract separation of pulmonary artery, expression of SoX4 in cushions and myocardium. Then how is it responsible for autoimmunity?

Humans have immune system which can recognize pathogens such as bacteria, fungi, virus etc. it can eliminate them and resist the possible infectious disease. T-lymphocytes or helper T-cells can identify pathogens and the infectious cells. The helper lymphocyte contains specialized lineage called T-regulatory or Treg that instead of helping to fight infection, it actually inhibits the response of normal lymphocytes. It has been observed that mice and humans without Treg cells develop a fatal autoimmune disease caused by T-helper cell’s uncontrolled attack on the body’s own cells.

Now the scientists have found that Foxp3 protein is responsible for the development and functioning of Treg cells. They found that removing this protein gene from the genomic DNA prevents development of Treg cells. But Foxp3 protein does not work alone, it work as a part of complex proteins that help regulate the work of genes that are important for functioning of Treg cells. That set of proteins include Foxp1.

Scientists at Higher School of Economics, the institute of bioorganic chemistry of Russian academy of science and the memorial Sloan Kettering cancer center created a genetic model that helps to understand the nature of this protein. The study has been carried out under the guidance of Aleksander Rudensky and genetic model was created to explain exactly how foxp1 protein affects foxp3. They began by removing part of the Foxp1 gene in Treg from laboratory mice. The comparison of the normal cells with the cell in which foxp1 was removed has been studied. The study revealed that Foxp3 is much worse at bonding DNA in absence of Foxp1. Hence if Foxp3 is essential for Treg, then Foxp1 also has great importance because removal of that protein causes a negative effect on foxp3 mechanism. Therefore according to the research foxp3 and foxp1 are the keys to create the drugs that can selectively affect the Treg cells.

Also cancerous tumors attract Treg cells to defend themselves against body’s immune system. The ore Treg cells present in the tumor, the worst the patient’s prognosis. Hence if we could control the quantity and activity of the Treg cells then we can create effective medicines for incurable illness.

]]>Recent years have witnessed significant efforts toward the development of mini-organs known as organoids in the culture dish. Basically, organoids are tiny, self-organized, 3-D tissue cultures that are derived from stem cells. Organoids contain various cell variants and complex microarchitectures present in human organs like kidney, liver, intestine, and even the brain. They are designed to replicate the complexity of an organ or to express selected functions of it like producing only certain types of cells.

The challenge

Most of the mini organs grown in vitro lack vasculature necessary to provide oxygen and nutrients, remove metabolic waste, and facilitate communication between different cell types that results in their maturation into truly functional tissue building blocks.

What is new

Now, a collaborative team of researchers have developed a new method of organoid development. Researchers subjected the stem cell-derived organoids to fluidic shear strain, they found significantly enlarge organoid-derived vascular networks and improved maturation of kidney compartments in comparison to previous static culture methods. The work is published in Nature Methods.

“While our organoids and those generated in other laboratories contained large numbers of well-organized nephrons and primitive blood vessels, they still lacked pervasive vascular compartments with perfusable lumens,” said co-corresponding author Morizane, M.D., Ph.D., Assistant Professor at Brigham and Women’s Hospital and Harvard Medical School (HMS), and a member of the Harvard Stem Cell Institute.

Researchers across the globe used to mature kidney organoids by implanting them into animals where they can associate to the host’s vasculature in vivo.

“For the first time, our study demonstrates that by exposing growing organoids to fluid flow, a mechanical cue known to play an important role for tissue development in the body, we can greatly enhance their vascularization and maturation in vitro,” said Morizane.

What they did

The research team used expertise from the Lewis lab that has established procedures to create vascularized human tissues, using 3D bioprinting that can be perfused and sustained for a long time span. Based on these findings, the researchers hypothesized that fluid flow could also promote the formation of blood vessels from precursor endothelial cells found in growing kidney organoids.

“We determined the right combination of underlying extracellular matrix, media additives, and fluidic shear stress under which human stem-cell derived organoids would flourish when grown in our 3D-printed millifluidic chips,” said Kimberly Homan, Ph.D., who is a first author on the study and working as Research Associate in Lewis’ group at the Wyss Institute and SEAS.

The vessels growing on the 3D-printed chips form an intermeshed network with open lumens, which can be perfused with fluids as confirmed by directly imaging fluorescent beads moving freely through them.

Vascular bed at the edge of a kidney organoid

“The vascular networks form close to the epithelial structures that build the glomerular and tubular compartments, and in turn promote epithelial maturation. This integrated process works really like a two-way street”, added Navin Gupta a Clinical Research Fellow working on Morizane’s team at the Brigham

Why it matters

Latest findings can open new ways for precisely testing drug toxicity in vitro in differentiated nephron compartments and modeling kidney diseases, like polycystic kidney disease, that affect specific structures. It may also pave the way to vascularize other types of organoids, such as the liver organoids.

“This study is a great example of the importance of mechanobiology and the potential power of the Wyss Institute’s 3D Organ Engineering Initiative. It provides an important cornerstone for many efforts that aim to create functional human tissues de novo for research, pharmaceutical and tissue regenerative applications,” said Wyss Institute Founding Director Donald Ingber.

The study was funded by the National Institutes of Health, Harvard’s Wyss Institute for Biologically Inspired Engineering, and the Harvard Stem Cell Institute.

]]>https://thebioscientist.org/2019/02/12/new-method-growing-kidney-organoids/feed/02376Researchers develop pill that could replace insulin injectionshttps://thebioscientist.org/2019/02/08/researchers-develop-pill-replace-insulin-injections/ https://thebioscientist.org/2019/02/08/researchers-develop-pill-replace-insulin-injections/#respondFri, 08 Feb 2019 09:52:49 +0000https://thebioscientist.org/?p=2372MIT-led research team may have found a futuristic solution by developing a drug capsule that could be used to deliver insulin orally,.

]]>February 08, 2019: Millions of people across the globe live with diabetes or know someone having diabetes. It’s a condition where the human body either doesn’t produce enough insulin or respond properly to it. Insulin is important because it acts as a “key” which allows glucose movement from blood to the body’s cells. In the case of diabetes, the patient has to inject themselves with insulin shots on regular basis.

Now an MIT-led research team may have found a futuristic solution by developing a drug capsule that could be used to deliver insulin orally, potentially substituting the need of insulin injections that people with type 2 diabetes have to give themselves.

This blueberry sized capsule contains a small needle made up of compressed insulin, which is infused after the capsule reaches the stomach. In tests in animals, researchers demonstrated the pill’s ability to deliver enough insulin to lower blood sugar to levels comparable to those produced by injection shots of Insulin. They also showed that the device can be adapted to deliver other protein drugs.

“We are really hopeful that this new type of capsule could someday help diabetic patients and perhaps anyone who requires therapies that can now only be given by injection or infusion,” says Robert Langer, the David H. Koch Institute Professor, a member of MIT’s Koch Institute for Integrative Cancer Research, and one of the senior authors of the study.

Researchers developed a pill coated with just one needle in order to avoid injecting drugs into the interior of the stomach, where stomach acids would break them before showing any effect. The tip of the needle is made of almost 100 percent compressed, freeze-dried insulin, using the same process used to form tablets of medicine. It also consists of a needle shaft which does not enter the stomach wall, is made from another biodegradable material.

Within the capsule, the needle is attached to a compressed spring that is held in place by a disk made of sugar. When the capsule is swallowed, water in the stomach dissolves the sugar disk, releasing the spring and injecting the needle into the stomach wall. The stomach wall has no pain receptors, so the researchers believe that patients would not be able to feel the injection.

Self-orientation

It is important that the needle remains in contact with the lining of the stomach, to ensure that the drug is injected into the stomach wall. Taking inspirations from leopard tortoise having self-orientation feature, researchers designed pill’s shell in a such a manner that no matter how the capsule lands in the stomach, it can orient itself from any position. The researchers used computer modeling to come up with a solution of curvature of the pill’s shell, which allows it to reorient itself even in the dynamic environment of the stomach.

“As soon as you take it, you want the system to self-right so that you can ensure contact with the tissue,” Traverso says.

Once the tip of the needle is injected into the stomach wall, the pill takes roughly an hour to release insulin into the bloodstreams. After releasing insulin, the pill (made from biodegradable polymer and stainless-steel components) can pass through the digestive tract without causing any harm.

“What’s important is that we have the needle in contact with the tissue when it is injected,” Abramson says. “Also, if a person were to move around or the stomach was to growl, the device would not move from its preferred orientation.”

During tests in pigs, the researchers were able to successfully deliver up to 300 micrograms of insulin. More recently, they successfully increased the dose to 5 milligrams, which is comparable to the amount that a patient with type 2 diabetes would need to inject.

“Our motivation is to make it easier for patients to take medication, particularly medications that require an injection,” Traverso says. “The classic one is insulin, but there are many others.”

The MIT team is currently working with Novo Nordisk to further develop the technology and optimize the manufacturing process for the capsules. Researchers believe this type of drug delivery could be useful for any protein drug that normally has to be injected. It may also work for nucleic acids such as DNA and RNA.

]]>https://thebioscientist.org/2019/02/08/researchers-develop-pill-replace-insulin-injections/feed/02372Researchers Discover Bees Can Do Basic Arithmetichttps://thebioscientist.org/2019/02/07/researchers-discover-bees-basic-arithmetic/ https://thebioscientist.org/2019/02/07/researchers-discover-bees-basic-arithmetic/#respondThu, 07 Feb 2019 06:26:29 +0000https://thebioscientist.org/?p=2363Researchers have found bees can do basic mathematics, in a discovery that expands our understanding of the brain size and brain power.

]]>Researchers have found bees can do basic mathematics, in a discovery that expands our understanding of the relationship between brain size and brain power.

Building on their finding that honeybees can understand the concept of zero, Australian and French researchers set out to test whether bees could perform arithmetic operations like addition and subtraction.

Solving maths problems requires a sophisticated level of cognition, involving the complex mental management of numbers, long-term rules and short term working memory.

The revelation that even the miniature brain of a honeybee can grasp basic mathematical operations has implications for the future development of Artificial Intelligence, particularly in improving rapid learning.

Led by researchers from RMIT University in Melbourne, Australia, the new study showed bees can be taught to recognise colours as symbolic representations for addition and subtraction, and that they can use this information to solve arithmetic problems.

RMIT’s Associate Professor Adrian Dyer said numerical operations like addition and subtraction are complex because they require two levels of processing.

“You need to be able to hold the rules around adding and subtracting in your long-term memory, while mentally manipulating a set of given numbers in your short-term memory,” Dyer said.

“On top of this, our bees also used their short-term memories to solve arithmetic problems, as they learned to recognize plus or minus as abstract concepts rather than being given visual aids.

“Our findings suggest that advanced numerical cognition may be found much more widely in nature among non-human animals than previously suspected.

“If maths doesn’t require a massive brain, there might also be new ways for us to incorporate interactions of both long-term rules and working memory into designs to improve rapid AI learning of new problems.”

There is considerable debate around whether animals know or can learn complex number skills.

Many species can understand the difference between quantities and use this to forage, make decisions and solve problems. But numerical cognition, such as the exact number and arithmetic operations, requires a more sophisticated level of processing.

Previous studies have shown some primates, birds, babies and even spiders can add and/or subtract. The new research, published in Science Advances, adds bees to that list.

The bees received a reward of sugar water when they made a correct choice in the maze and received a bitter-tasting quinine solution if the choice was incorrect.

Honeybees will go back to a place if the location provides a good source of food, so the bees returned repeatedly to the experimental set-up to collect nutrition and continue learning.

When a bee flew into the entrance of the maze they would see a set of elements, between 1 to 5 shapes.

The shapes were either blue, which meant the bee had to add, or yellow, which meant the bee had to subtract.

After viewing the initial number, the bee would fly through a hole into a decision chamber where it could choose to fly to the left or right side of the maze.

One side had an incorrect solution to the problem and the other side had the correct solution of either plus or minus one. The correct answer was changed randomly throughout the experiment to avoid bees learning to visit just one side of the maze.

At the beginning of the experiment, bees made random choices until they could work out how to solve the problem. Eventually, over 100 learning trials that took 4 to 7 hours, bees learned that blue meant +1, while yellow meant -1. The bees could then apply the rules to new numbers.

Scarlett Howard said the ability to do basic maths has been vital in the flourishing of human societies historically, with evidence that the Egyptians and Babylonians used arithmetic around 2000BC.

“These days, we learn as children that a plus symbol means you need to add two or more quantities, while a minus symbol means you subtract,” she said.

“Our findings show that the complex understanding of maths symbols as a language is something that many brains can probably achieve, and helps explain how many human cultures independently developed numeracy skills.”

]]>In a study with significant implications for human organ transplantation, researchers have successfully grown functional mouse kidneys inside rats from just a few donor stem cells.

The results of the study, led by researchers from the National Institute for Physiological Sciences in Japan, will be published in an upcoming issue of Nature Communications.

For patients with end-stage renal disease, a kidney transplant is the only hope for regaining quality of life. Yet many of these patients will never undergo transplant surgery thanks to a chronic shortage of donor kidneys. With 95,000 patients on the waiting list for a donor kidney in the United States alone, demand far outstrips supply.

But researchers have been working on ways to grow healthy organs outside the human body. One such method, called blastocyst complementation, has already produced promising results. Researchers take blastocysts, the clusters of cells formed several days after egg fertilization, from mutant animals missing specific organs and inject them with stem cells from a normal donor, not necessarily of the same species. The stem cells then differentiate to form the entire missing organ in the resulting animal. The new organ retains the characteristics of the original stem cell donor, and can thus potentially be used in transplantation therapy.

“We previously used blastocyst complementation to generate rat pancreas in apancreatic mutant mice,” explains lead author of the new study Teppei Goto. “We, therefore, decided to investigate whether the method could be used to generate functional kidneys, which would have much greater application in regenerative medicine owing to the high donor demand.”

Initial attempts by the researchers to grow rat kidneys in mice proved unsuccessful, as rat stem cells did not readily differentiate into the two main types of cells needed for kidney formation. However, when the reverse scenario was attempted, mouse stem cells efficiently differentiated inside rat blastocysts, forming the basic structures of a kidney.

A diagram of method and result. (Credit: NIPS)

After being implanted into pseudo-pregnant rats, the complemented blastocysts matured into normal fetuses. Remarkably, more than two-thirds of the resulting rat neonates contained a pair of kidneys derived from the mouse stem cells. Further screening showed that all of the kidneys were structurally intact, and at least half could potentially produce urine.

“Our findings confirm that interspecific blastocyst complementation is a viable method for kidney generation,” says study corresponding author Masumi Hirabayashi. “In the future, this approach could be used to generate human stem cell-derived organs in livestock, potentially extending the lifespan and improving the quality of life of millions of people worldwide.”

]]>https://thebioscientist.org/2019/02/06/scientists-one-step-closer-to-growing-made-to-order-human-kidneys/feed/02355Diversity in the CD4 receptor protects chimpanzees from infection by AIDS-like viruseshttps://thebioscientist.org/2019/02/05/diversity-in-the-cd4-receptor-protects-chimpanzees-from-infection-by-aids/ https://thebioscientist.org/2019/02/05/diversity-in-the-cd4-receptor-protects-chimpanzees-from-infection-by-aids/#respondTue, 05 Feb 2019 08:22:17 +0000https://thebioscientist.org/?p=2302Scientists found that the CD4 surface protein, used by HIV and SIV as the receptor to enter immune cells, is highly variable.

]]>Beatrice H. Hahn, MD, a professor of Medicine and Microbiology in the Perelman School of Medicine at the University of Pennsylvania, and her colleagues have been studying the origin of HIV-1 in non-human primates for decades. They previously discovered that simian immunodeficiency viruses (SIVs) infecting wild-living chimpanzees and gorillas jumped the species barrier into humans on four occasions, one of which spawned the AIDS pandemic. Understanding how these viruses are transmitted within and between species may reveal clues for novel vaccine strategies in humans.

HIV and SIV infect and kill immune cells called CD4 T cells, a process that ultimately leads to AIDS. Publishing this week in the Proceedings of the National Academy of Sciences, Hahn’s lab and an international team of collaborators, found that the CD4 surface protein, which is used by HIV and SIV as the receptor to enter immune cells, is highly variable among wild chimpanzees. Characterizing fecal samples from over 500 chimpanzees across sub-Saharan Africa, they found, to their surprise, nine CD4 variants. They went on to demonstrate that this diversity in CD4 protects chimpanzees from their own strain of SIV, as well as potentially dangerous SIVs carried by other monkey species on which they prey.

SIVs infect over 40 primate species in sub-Saharan Africa and can be deadly. Hahn’s group showed in previous studies that SIV-infected chimpanzees in the wild have higher mortality than uninfected chimpanzees and can develop an AIDS-like disease, like that in humans.

“CD4 is known to have evolved rapidly in primates, but the reason for this has remained unclear,” said Hahn. “Now we find that mutations in the chimpanzee CD4 reduce susceptibility to SIV infection, which could provide a selective advantage to apes bearing these CD4 variants.”

To get into host cells, HIV and SIV use their outermost, or envelope, glycoprotein to bind to the outermost region of the CD4 receptor. “To counteract this, chimpanzees have evolved several mutations in this CD4 domain that blocks this interaction,” said co-first author Ronnie Russell, a doctoral student in Hahn’s lab.

The team found that these mutations include amino acid changes in contact residues as well as the addition of bulky sugar molecules, called glycans, at the CD4-envelope binding interface. “Glycans on the chimpanzee CD4 clash with glycans on the SIV envelope, which impedes virus entry into the cell,” said co-first author Frederic Bibollet-Ruche, Ph.D., a research assistant professor of Microbiology in Hahn’s lab. This type of glycan-glycan interaction has not been seen before as an antiviral mechanism.

Unlike chimps, humans lack protective glycans on the virus-binding domain of the CD4 protein. “This may explain our relative susceptibility to SIV cross-species infection, which has occurred at least a dozen times within the last century or so,” said co-author Paul Sharp, Ph.D., an evolutionary biologist at the University of Edinburgh.

Although chimpanzee SIVs are highly divergent from their human counterparts, previous work by the Hahn group showed that they share unexpected antibody cross-reactivity with HIV at the very tip, or apex, of their envelope spike. This finding raised the possibility that HIV and SIV envelopes could be used in combination to focus a protective antibody response to this conserved epitope in a vaccine.

“Understanding how the diversification of the chimpanzee CD4 affects the structure and function of the chimpanzee SIV envelope has practical implications for AIDS vaccine development,” says co-author George Shaw, MD, Ph.D., a professor of Medicine and Microbiology at Penn.

The research consortium that carried out this work included primatologists dedicated to the conservation of wild chimpanzees. “The many samples provided by our collaborators have been instrumental in uncovering the tricks that chimpanzees use to ward off SIV,” said Hahn. “Ultimately, this may help in the design of better HIV vaccines. It’s a long shot, but it has certainly brought all our work on the biology and evolution of the ape precursors of HIV full circle.”

]]>https://thebioscientist.org/2019/02/05/diversity-in-the-cd4-receptor-protects-chimpanzees-from-infection-by-aids/feed/02302Stopping melanoma by cutting off the blood supplyhttps://thebioscientist.org/2019/01/05/stopping-melanoma-by-cutting-off-the-blood-supply/ https://thebioscientist.org/2019/01/05/stopping-melanoma-by-cutting-off-the-blood-supply/#respondSat, 05 Jan 2019 15:55:46 +0000https://thebioscientist.org/?p=2292Preventing melanoma from spreading to different parts of the body may be as simple as removing the blood supply to cancer

]]>Preventing melanoma from spreading to different parts of the body may be as simple as removing the blood supply to the cancer, as per the researchers.

Researchers from The University of Queensland’s Diamantina Institute have found stem cells which are responsible for forming blood vessels in tumours and have recognized how to ‘turn the cells off’.

Professor Kiarash Khosrotehrani said the latest findings had enormous implications for cancer patients.

“Blood vessels are vital because tumours can’t grow without them – they feed the tumours and allow the cancer to spread,” Professor Khosrotehrani said.

“If you get rid of these stem cells, then the blood vessels don’t form and the tumours don’t grow or spread to other locations.”

Professor Khosrotehrani said ability to obstruct blood vessel progression could be valuable in treating recently diagnosed cancer patients as it may help to halt the cancer from spreading at an early phase.

“This idea has been around for a while, but it has proven difficult to achieve because blood vessel formation is a fundamental mechanism by which our body responds to injury,” he said.

“Directly targeting the stem cells that form these blood vessels is a new approach that could make the difference.”

Researcher Dr Jatin Patel told that melanoma’s ability to rapidly spread from the skin to other parts of the body was what made it so lethal.

“We know that before tumours spread to places like lymph nodes or lungs, the body starts growing extra blood vessels in these areas – almost as if preparing special ‘niches’ for the cancer,” Dr Patel said.

“Our next study will focus on blocking the development of these niches.

]]>According to the current statistics, about 12% of women have a lifetime risk of developing breast cancer. In recent years, there’s been an eruption amongst the oncologists and associated scientific community, on discovering life-saving treatment advances against breast cancer. The measures till now discovered for its cure are — surgery, radiation, hormonal (anti-estrogen) therapy, and/or chemotherapy.

Scientists from Stevens Institute of Technology have developed a novel molecule which utilizes an unknown mechanism to target breast cancer cells, especially for the patients with drug-resistant or severe metastatic stages of the disease.

Abhishek Sharma, a chemistry professor at Stevens, classified this new molecule to the class of drugs that degrade estrogen receptors, proteins inside cells that have been proven to be the most significant target in breast cancer medication over the last 30 years.

“The unique benefit of our compounds is that this is a fundamentally different type of structure that was previously not known to degrade or inhibit estrogen receptors,” said Sharma, whose work was recently published in the journal ACS Medicinal Chemistry Letters. “It’s not a tweak of an existing drug; it works in a completely different way.”

Due to the increasing demand and various clinical applications of such drugs called Selective Estrogen Receptor Degraders (SERDs), various pharmaceutical companies have endowed much of their time in developing them and to remodel their structure.

In the majority of cases, breast cancer tumors gain resistance towards these drugs, as a consequence of which patients are given high dose chemotherapies to prevent cancer from escalating. The setback of SERDs is that they are difficult to formulate into pills, because of which patients are given large painful injections directly into their muscles. More recently, drugs have failed in clinical trials because of side effects.

In addition to Abhishek’s team, many cancer biologists and physicians at Memorial Sloan Kettering Cancer Center in New York and at the University of Illinois were looking ahead to investigate a better way to treat breast cancer, which protects one in eight U.S. women and tens of millions of women worldwide.

For their study, they considered a molecule which serves as a “homing device” for estrogen receptors and to that they attached a series of experimental side-chain compounds known as degrons. Once this homing device was attached to the estrogen receptor, it was degraded by the degrons by hijacking tumor cell’s protein-disposal machinery and routing it to the receptor.

For weeks and months, scientists experimented to formulate several combinations with this homing device. They tested more than a dozen of them and observed their interaction with the cancer cells’ estrogen receptors. These new molecules were easily delivered. They not just deteriorated the estrogen receptors but also inhibited various signals that lead to cell progression, and also blocking the hormone estrogen from binding to it.

“We consider these results to be very promising,” said Sharma. “This is a novel molecular structure, and several analogs produced excellent early activity.”

Further next, Stevens team will further look forward to identify potential and promising compounds that develops them into more potent drug to be investigated in mouse models.

]]>In a recent research, it has been suspected that Durvalumab (an anti-cancer immunotherapy), may interfere with the ability of tumor cells to grow and spread. Durvalumab is an antineoplastic drug and an immune checkpoint inhibitor that has received approval in February by United States Food and Drug Administration (FDA) as a new strategy for treating patients in their stage 3 of non-small cell lung cancer.

Researchers at Moffitt Cancer Center, have investigated the increase in lifespan of patients suffering from the third stage of lung cancer when their treatment included durvalumab following platinum-based chemotherapy. The research has been published in the New England Journal of Medicine.

Initially, in 2017, Durvalumab manufactured by AstraZeneca received approval by FDA for metastatic bladder cancer. However, chair of the Department of Thoracic Oncology at Moffitt, Scott Antonia, M. D., PhD., threw light upon the potential of durvalumab to serve as a treatment therapy for advanced non-small cell lung cancer patients. Working with AstraZeneca, he launched the PACIFIC clinical trial, a randomized, double-blind, placebo-controlled international phase 3 trial that spanned 235 investigative sites in 26 countries and enrolled more than 700 patients.

Approximately one-third of patients with non-small cell lung cancer have advanced stage 3 disease at the time of diagnosis. Standard treatment has been chemotherapy and radiation, but 85 percent of patients do not respond to the therapy,” said Antonia. “Adding durvalumab to the standard treatment has made a big impact for this group of patients. It’s allowing them to live longer and potentially increasing their chance for cure.

Based on two-year follow-up of patients, new clinical trial data concludes that giving Durvalumab with radiation therapy may work better in treating patients with non-small cell lung cancer and it shows promising results in increasing the survival rate of the lung cancer patients as compared to placebo on their treatment with this anti-cancerous drug.